Interleukin-2 (IL-2) stimulates both activated CD4⁺ and CD8⁺ T cells to proliferate. IL-2 signals through an identical receptor complex and promotes the same dose-dependent phosphorylation of the canonical transcription factor STAT5 in both cell types. Despite this, CD8⁺ T cells enter the S phase earlier and proliferate to a greater extent than do CD4⁺ T cells in response to IL-2. We identified distinct IL-2 signaling dynamics in CD4⁺ and CD8⁺ T cells. In IL-2–stimulated CD8⁺ T cells, STAT5 phosphorylation increased rapidly and was sustained for 6 hours. In contrast, CD4⁺ T cells had a biphasic response, with maxima at 15 min and 2 to 4 hours after stimulation. Both cell types required vesicular trafficking, but only CD4⁺ T cells required new protein synthesis to maintain high phosphorylation of STAT5. Two subunits of the IL-2 receptor, IL-2Rβ and IL-2Rγ, were twice as abundant in CD8⁺ T cells than in CD4⁺ T cells. Reduction of IL-2Rβ abundance by 50% was sufficient to convert CD8⁺ T cells to a CD4⁺ T cell–like signaling pattern and delay S phase entry. These results suggest that the larger pool of IL-2Rβ chains in CD8⁺ T cells is required to sustain IL-2 signaling and contributes to the quantitatively greater proliferative response to IL-2 relative to that of CD4⁺ T cells. This cell type–specific difference in IL-2Rβ abundance appears to tune responses, potentially preventing extensive, autoimmune proliferation of CD4⁺ T cells, while still enabling sufficient proliferation of CD8⁺ T cells to control viral infections.

白细胞介素 2 (IL-2) 刺激活化的 CD4 ⁺和 CD8 ⁺ T 细胞增殖。IL-2 通过相同的受体复合物发出信号，并促进两种细胞类型中经典转录因子 STAT5 的相同剂量依赖性磷酸化。尽管如此，CD8 ^{+ T 细胞比 CD4 +} T 细胞响应 IL-2更早地进入 S 期并且增殖程度更高。^{我们确定了 CD4 +}和 CD8 ⁺ T 细胞中不同的 IL-2 信号动力学。在 IL-2 刺激的 CD8 ⁺ T 细胞中，STAT5 磷酸化迅速增加并持续 6 小时。相比之下，CD4 ⁺T 细胞具有双相反应，在刺激后 15 分钟和 2 至 4 小时达到最大值。两种细胞类型都需要囊泡运输，但只有 CD4 ⁺ T 细胞需要新的蛋白质合成来维持 STAT5 的高磷酸化。^{IL-2 受体的两个亚基 IL-2Rβ 和 IL-2Rγ 在 CD8 +} T 细胞中的丰度是 CD4 ⁺ T 细胞中的两倍。IL-2Rβ 丰度降低 50% 足以将 CD8 ⁺ T 细胞转化为 CD4 ⁺ T 细胞样信号模式并延迟 S 期进入。这些结果表明 CD8 ^{+中较大的 IL-2Rβ 链池相对于 CD4 +} T 细胞，T 细胞需要维持 IL-2 信号传导，并有助于在数量上对 IL-2 产生更大的增殖反应。这种细胞类型特异性 IL-2Rβ 丰度差异似乎可以调节反应，可能阻止 CD4 ⁺ T 细胞广泛的自身免疫增殖，同时仍使 CD8 ⁺ T 细胞充分增殖以控制病毒感染。